US2019062424A1PendingUtilityA1

Vegf/dll4 binding agents and uses thereof

68
Assignee: ONCOMED PHARM INCPriority: Sep 23, 2011Filed: Aug 29, 2018Published: Feb 28, 2019
Est. expirySep 23, 2031(~5.2 yrs left)· nominal 20-yr term from priority
Inventors:Austin GurneyAaron SatoChristopher J. Bond
A61P 35/02A61P 35/00C07K 2317/73C07K 16/22C07K 16/28C07K 2317/31A61K 2039/505A61K 45/06C07K 2317/76A61K 31/7068A61K 31/4745C07K 2317/92C07K 16/3046A61K 39/3955A61K 39/395C07K 16/303C07K 2317/56C07K 2317/565C07K 2317/24A61K 45/00C07K 16/18C07K 16/30A61K 39/00
68
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Claims

Abstract

The present invention relates to VEGF-binding agents, DLL4-binding agents, VEGF/DLL4 bispecific binding agents, and methods of using the agents for treating diseases such as cancer. The present invention provides antibodies that specifically bind human VEGF, antibodies that specifically bind human DLL4, and bispecific antibodies that specifically bind human VEGF and/or human DLL4. The present invention further provides methods of using the agents to inhibit tumor growth. Also described are methods of treating cancer comprising administering a therapeutically effect amount of an agent or antibody of the present invention to a patient having a tumor or cancer.

Claims

exact text as granted — not AI-modified
1 - 89 . (canceled) 
     
     
         90 . A method of inhibiting colorectal tumor growth in a subject, comprising administering to the subject a therapeutically effective amount of a modified immunoglobulin molecule comprising a first antigen-binding site that specifically binds human vascular endothelial growth factor (VEGF) and a second antigen-binding site that specifically binds human delta-like ligand 4 (DLL4), in combination with irinotecan. 
     
     
         91 . The method of  claim 90 , wherein:
 the first antigen-binding site comprises a heavy chain CDR1 comprising NYWMH (SEQ ID NO:17), a heavy chain CDR2 comprising DINPSNGRTSYKEKFKR (SEQ ID NO:18), and a heavy chain CDR3 comprising HYDDKYYPLMDY (SEQ ID NO:19);   the second antigen-binding site comprises a heavy chain CDR1 comprising TAYYIH (SEQ ID NO:13) or AYYIH (SEQ ID NO:79), a heavy chain CDR2 comprising YIANYNRATNYNQKFKG (SEQ ID NO:14), YISSYNGATNYNQKFKG (SEQ ID NO:15), YIAGYKDATNYNQKFKG (SEQ ID NO:59), or YISNYNRATNYNQKFKG (SEQ ID NO:65), and a heavy chain CDR3 comprising RDYDYDVGMDY (SEQ ID NO:16); and   both the first and second antigen-binding sites comprise a light chain CDR1 comprising RASESVDNYGISFMK (SEQ ID NO:20), a light chain CDR2 comprising AASNQGS (SEQ ID NO:21), and a light chain CDR3 comprising QQSKEVPWTFGG (SEQ ID NO:22).   
     
     
         92 . The method of  claim 91 , wherein the second antigen-binding site comprises a heavy chain CDR1 comprising TAYYIH (SEQ ID NO:13). 
     
     
         93 . The method of  claim 91 , wherein the second antigen-binding site comprises a heavy chain CDR2 comprising YISNYNRATNYNQKFKG (SEQ ID NO:65). 
     
     
         94 . The method of  claim 91 , wherein the second antigen-binding site comprises a heavy chain CDR1 comprising TAYYIH (SEQ ID NO:13) and a heavy chain CDR2 comprising YISNYNRATNYNQKFKG (SEQ ID NO:65). 
     
     
         95 . The method of  claim 91 , wherein the first antigen-binding site comprises a heavy chain variable region comprising SEQ ID NO:11. 
     
     
         96 . The method of  claim 91 , wherein the second antigen-binding site comprises a heavy chain variable region comprising SEQ ID NO:64. 
     
     
         97 . The method of  claim 91 , wherein both the first and second antigen-binding sites comprise a light chain variable region comprising SEQ ID NO:12. 
     
     
         98 . The method of  claim 91 , wherein the first antigen-binding site comprises a heavy chain variable region comprising SEQ ID NO:11 and a light chain variable region comprising SEQ ID NO:12, and the second antigen-binding site comprises a heavy chain variable region comprising SEQ ID NO:64 and a light chain variable region comprising SEQ ID NO:12. 
     
     
         99 . The method of  claim 90 , wherein the modified immunoglobulin molecule is an antibody fragment. 
     
     
         100 . The method of  claim 90 , wherein the modified immunoglobulin molecule is a dual variable domain antibody. 
     
     
         101 . The method of  claim 90 , wherein the modified immunoglobulin molecule is a bispecific antibody. 
     
     
         102 . The method of  claim 90 , wherein the modified immunoglobulin molecule and irinotecan are administered sequentially to the subject. 
     
     
         103 . The method of  claim 90 , wherein the modified immunoglobulin molecule and irinotecan are administered concurrently to the subject. 
     
     
         104 . The method of  claim 90 , wherein the subject is human. 
     
     
         105 . A method of treating colorectal cancer in a subject, comprising administering to the subject a therapeutically effective amount of a modified immunoglobulin molecule comprising a first antigen-binding site that specifically binds human VEGF and a second antigen-binding site that specifically binds human DLL4, in combination with irinotecan. 
     
     
         106 . The method of  claim 105 , wherein:
 the first antigen-binding site comprises a heavy chain CDR1 comprising NYWMH (SEQ ID NO:17), a heavy chain CDR2 comprising DINPSNGRTSYKEKFKR (SEQ ID NO:18), and a heavy chain CDR3 comprising HYDDKYYPLMDY (SEQ ID NO:19);   the second antigen-binding site comprises a heavy chain CDR1 comprising TAYYIH (SEQ ID NO:13) or AYYIH (SEQ ID NO:79), a heavy chain CDR2 comprising YIANYNRATNYNQKFKG (SEQ ID NO:14), YISSYNGATNYNQKFKG (SEQ ID NO:15), YIAGYKDATNYNQKFKG (SEQ ID NO:59), or YISNYNRATNYNQKFKG (SEQ ID NO:65), and a heavy chain CDR3 comprising RDYDYDVGMDY (SEQ ID NO:16); and   both the first and second antigen-binding sites comprise a light chain CDR1 comprising RASESVDNYGISFMK (SEQ ID NO:20), a light chain CDR2 comprising AASNQGS (SEQ ID NO:21), and a light chain CDR3 comprising QQSKEVPWTFGG (SEQ ID NO:22).   
     
     
         107 . The method of  claim 106 , wherein the second antigen-binding site comprises a heavy chain CDR1 comprising TAYYIH (SEQ ID NO:13). 
     
     
         108 . The method of  claim 106 , wherein the second antigen-binding site comprises a heavy chain CDR2 comprising YISNYNRATNYNQKFKG (SEQ ID NO:65). 
     
     
         109 . The method of  claim 106 , wherein the second antigen-binding site comprises a heavy chain CDR1 comprising TAYYIH (SEQ ID NO:13) and a heavy chain CDR2 comprising YISNYNRATNYNQKFKG (SEQ ID NO:65). 
     
     
         110 . The method of  claim 106 , wherein the first antigen-binding site comprises a heavy chain variable region comprising SEQ ID NO:11. 
     
     
         111 . The method of  claim 106 , wherein the second antigen-binding site comprises a heavy chain variable region comprising SEQ ID NO:64. 
     
     
         112 . The method of  claim 106 , wherein both the first and second antigen-binding sites comprise a light chain variable region comprising SEQ ID NO:12. 
     
     
         113 . The method of  claim 106 , wherein the first antigen-binding site comprises a heavy chain variable region comprising SEQ ID NO:11 and a light chain variable region comprising SEQ ID NO:12, and the second antigen-binding site comprises a heavy chain variable region comprising SEQ ID NO:64 and a light chain variable region comprising SEQ ID NO:12. 
     
     
         114 . The method of  claim 105 , wherein the modified immunoglobulin molecule is an antibody fragment. 
     
     
         115 . The method of  claim 105 , wherein the modified immunoglobulin molecule is a dual variable domain antibody. 
     
     
         116 . The method of  claim 105 , wherein the modified immunoglobulin molecule is a bispecific antibody. 
     
     
         117 . The method of  claim 105 , wherein the modified immunoglobulin molecule and irinotecan are administered sequentially to the subject. 
     
     
         118 . The method of  claim 105 , wherein the modified immunoglobulin molecule and irinotecan are administered concurrently to the subject. 
     
     
         119 . The method of  claim 105 , wherein the subject is human.

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